Lecture 5 2/1/24

Question 1

Why must lipid-soluble drugs be metabolized to water-soluble substances?

Answer 1

-lipid-soluble, pharmacologically active drugs tend to be lipophilic and protein-bound
-these characteristics do not favor renal elimination

Question 2

What are the characteristics of phase 1 hepatic metabolism?

Answer 2

-makes molecules more polar
-involves oxidation, reduction, and hydrolysis

Question 3

What are the characteristics of phase 2 hepatic metabolism?

Answer 3

-makes molecules larger and more polar
-involves conjugation

Question 4

What are the characteristics of microsomal enzymes in hepatic metabolism?

Answer 4

-found in smooth ER
-non-specific and inducible
-mainly involved in oxidation and reduction in phase 1
-involved in glucuronide conjugation in phase 2

Question 5

What are the characteristics of non-microsomal enzymes in hepatic metabolism?

Answer 5

-found mainly in cytoplasm and mitochondria
-non-inducible
-mainly involved in hydrolysis in phase 1
-involved in all conjugations except glucuronide conjugation in phase 2

Question 6

What steps are involved in drug metabolism?

Answer 6

-inactivation of active compounds
-enzymatic induction and inhibition

Question 7

What is a prodrug?

Answer 7

a drug in which the metabolite has enhanced activity following drug metabolism

Question 8

What is high extraction hepatic metabolism?

Answer 8

-capacity to metabolize drug is very large
-inhibitors and inducers will not easily affect elimination and drug exposure

Question 9

What is low extraction hepatic metabolism?

Answer 9

-capacity to metabolize drug is low
-inhibitors or inducers will easily affect elimination and drug exposure

Question 10

What is the effect of induction?

Answer 10

action on enzymes that leads to the development of tolerance

Question 11

What factors affect drug metabolism?

Answer 11

-species and breed
-dose
-diet/nutritional status
-age
-diseases that alter blood flow/liver function
-gender

Question 12

Which phase of hepatic metabolism are cats deficient in?

Answer 12

phase 2/conjugation phase

Question 13

Why is it important that cats are deficient in bile salt export pump?

Answer 13

leads to less excretion in bile and more accumulation of some drugs

Question 14

What are the characteristics of enterohepatic recirculation?

Answer 14

-may occur if significant biliary excretion occurs
-often large molecules
-often after phase 2 metabolism